This application requests a 5-year renewal of the Center for Environmental Genetics (CEG). The unifying research focus of the Center is to study the impact of genetic diversity on individual susceptibility to deleterious environmental agents. The CEG has a long 15-year history of accomplishments in environmental genetics that helps shape one of the nation's current top priorities in environmental health sciences (EHS) research. The investigators will expand their pioneering efforts and propose the following aims for the next funding period. Aim 1: To promote research in gene-environment interactions in human health and disease by emphasizing the use of environmental exposures in relationship with genetic variations and epigenetic reprogramming to inform pathophysiologic endpoints. Aim 2: To hasten translation of basic biomedical EHS research and population-based studies into clinical practices for disease prevention, diagnosis, and prognosis. Reciprocally, Center activities will afford opportunities for novel hypotheses to be generated from human based studies to be tested in laboratory settings. Aim 3: To foster the development of sensitive pathophysiological markers for the assessment of internal dose and improve measures of body burden;to undertake the discovery predictive makers so that the effects of early life exposure on later-life disease risk could be anticipated and minimized through innovative intervention measures. Validation of these markers through quantitative and qualitative measurements of phenotype or clinical outcomes will be an integral part of this aim. Aim 4: To attract and train the next generation of biomedical EHS investigators and clinicians with a strong desire to apply EHS in their clinical practices through partnership of the investigators'comprehensive Career Development Program (CDP) and a newly established Master Degree in Clinical Training program. A Pilot Project Program will function to continue support young investigators till they attain independence in EHS research, and to recruit new-to-EHS scientists. Three Facility/Service Cores will facilitate attainment of the goals: 1) the Integrative Technology Services Core will inject leading edge technologies into EHS research;2) the Integrative Health Services Core will help manage and share epidemiological and clinical databases, support tissue procurement, and development of clinical protocols;and 3) the Informatics Core will support all levels of data-mining and hypothesis-creation opportunities from various systems biology and clinical investigations. The overarching objective of the Center is to improve human health through effective integration of basic, clinical and epidemiological research, germane to gene-environment interaction, toward the ultimate goal of delivering "personalized" medicine and devising public health initiatives for susceptible populations. The multiplicity of expertise and strong fund holding amongst membership, and the unyielding commitment from institution leadership constitute the elements of success in this application. BACKGROUND The University of Cincinnati, College of Medicine (UCMC) was established in 1819. The Kettering Laboratory of Applied Physiology at UCMC was established in 1930. In 1965, this Laboratory became the Department of Environmental Health (DEH). The Center for Environmental Genetics (CEG) is housed in the Department of Environmental Health at the University of Cincinnati, College of Medicine. This is the third competing continuation application for the University of Cincinnati Center for Environmental Genetics, funded initially in April 1992. The first Center Director was Dr. Daniel Nebert (1992-1997), the second was Dr. Marshall Anderson (1997-2005), the third (interim) was Dr. Alvaro Puga (2005-2006), and the fourth and current Director is Dr. Shuk-mei Ho (2006-present). There is a close collaboration between University of Cincinnati, College of Medicine and the Cincinnati Children's Medical Center (CCHMC);most members of the Center for Environmental Genetics have affiliations in these two Medical Centers. This application is a revised competing continuation application which includes changes suggested from the previous review. The theme of the Center for Environmental Genetics is to develop an understanding of the complex relationships between genetic susceptibility factors and environmental exposures, as well as alterations in genetic-epigenetic interplay under environmental influences, and to apply the understanding of these concepts to the study and alleviation of the pathogenesis of environmentally-induced diseases. The focus of the Center is to understand how exposure to environmental factors interacts with genes, genetic variants, and epigenetic modifiers, either to preserve health or to cause disease. ESSENTIAL CHARACTERISTICS Strategic Vision and Impact on Environmental Health